System neuroscienceA model of posttraumatic epilepsy induced by lateral fluid-percussion brain injury in rats
Section snippets
Experimental procedures
The study design is summarized in Fig. 1 and consisted of two independent experiments. In experiment 1, 18 animals subjected to lateral FPBI and 6 controls were monitored with video-electroencephalography (vEEG) at 7-week intervals beginning 7–9 weeks post-injury and continuing for 12 months. In experiment 2, 30 animals with TBI and 10 controls underwent more detailed vEEG monitoring every 4 weeks for 12 months. At the end of the experiments, all animals were killed and brains were collected
Mortality and apnea after lateral FPBI
Mortality rates in animals subjected to lateral FPBI were 33% and 31% in experiments 1 and 2, respectively, consistent with previous reports in which animals were subjected to severe TBI (McIntosh et al 1989, Thompson et al 2005). Animals that died immediately after FPBI or during the first week post-injury were included in statistical analysis of mortality, but excluded from other analyses. Animals that died prior to the first vEEG monitoring, dropped more than 20% of pre-injury body weight,
Discussion
TBI induced by lateral FPBI in rodents is currently the best characterized and most widely used preclinical model of human closed head injury (Thompson et al., 2005). The present experiments aimed to investigate whether severe, non-penetrating lateral FPBI in adult rats results in the development of epilepsy, to evaluate the characteristics of PTE syndrome in rats and to determine its adequacy as a model for human PTE.
Conclusions
We demonstrated that lateral FPBI in rats induces a PTE syndrome with electrographic, behavioral, and pathologic characteristics similar to those of human PTE. Strikingly similar data were obtained from the two independent experiments suggesting good reproducibility of the lateral FPBI model. A rat model of PTE that reproduces a wide range of clinical features of human PTE provides an excellent tool to study the mechanisms of posttraumatic epileptogenesis, investigate new therapeutic approaches
Acknowledgments
This study was supported by the Academy of Finland, Sigrid Juselius Foundation, Finnish Cultural Foundation, and Paulo Foundation to A.P.; NIH NS08803 and NS40978 to T.K.M.; Centre for International Mobility CIMO, European Concerted Action and Research in Epilepsy (EUCARE), World Federation of Neurology and Finnish Neurological Foundation to I.K.
We gratefully acknowledge the technical assistance of Rachel Hoover and Brent Witgen in helping to establish the lateral fluid-percussion brain injury
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